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Reflections from a Med Student


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#121 PTShapeShifter

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Posted 23 March 2013 - 11:08 AM

Here's another promising rat study of Sunifiram, which is said to be 1000X potency of piracetam. http://www.ncbi.nlm....pubmed/23295391

#122 NoopMed

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Posted 23 March 2013 - 10:40 PM

Hi all, has anyone either researched or tested two newly available racetam-like compound, supposedly much stronger than piracetam, called sunifram and uniform, both said to acts as a positive allosteric modulator of AMPA receptors -- see PubMed research abstract: http://www.ncbi.nlm.nih.gov/pubmed/18954993

According to research, sunifram acts on the receptors for glutamate is an important neurotransmitter that plays a key role in long-term potentiation and is important for learning and memory.

NoopMed, can you access the full article from the abstract listed in PubMed?

I may order some, but other's experience or further research insights may sway me, one way or another...?

Gratitudes in advance for any of your insight & comments left here.

PTShapeShifter



I was able to access the full articles for most of the articles cited on the wikipedia article regarding Sunifiram. I also reviewed several of the discussions elsewhere on this forum regarding this novel nootropic. It also appears newstarnootropics is selling this stuff.

The drug does indeed appear to stimulate a glutamate responsive receptor-- specifically the NMDA receptor type. It does this through positive allosteric modification by binding at the glycine binding site of NMDAR. This was the proposed mechanism as of 1/2013. An article from 2003 describes it as an AMPAkine (working on ampa glutamate receptors) but the newer data does not indicate this. Recall from dicussions here and elsewhere that the NMDA receptor is certainly involved in learning, but has been implicated in excitotoxicity through calcium influx and neuro apoptosis when neurons experience ischemia or other severe stress. Many nootropics employ the NMDA receptor, but I cant really comment on their potential for excitotoxicity as ive never encountered those specific studies.

Much like piracetam, it reverses drug indcued amnesia, etc, and appears to enahnce LTP and hippocampal memory formation.

The major issue to consider here is the concept of potency vs efficacy with drug pharmacology. Efficacy is the ability of a drug to induce a desired effect on cells. It is the measure of that effect intensity. In the case of nootropics we are looking for maximum memory or logic ability enhancement, drugs that achieve the highest level of this have the high efficacy and are the most efficacious. Most drugs have a maximum effective concentration where they peak in their ability to induce the desired effect. I havent seen articles specifically measuring this, but many people on this forum seem to agree that the racetams have bell-curve efficacy, meaning they are most effective in a goldilocks window, not too little, not too much-- just right. This is where potency comes in. If two drugs have the same efficacy, they can achieve the same effect at their optimal dose. But, one drug might be more POTENT, thus making its optiminal dose for ideal efficacy LOWER than a less potent drug. Aka, less drug is needed for the same effect.

In the case of Sunifiram, the data from rats shows it had similar efficacy to piracetam at the optiminal dose when measuring rat activity in various memory and behavior tests. Actually, it appears to be slightly less effective than piracetam, but still has a very siginificant effect. The remarkable thing was that the optimal dose was 1000x smaller than Piracetam. The effects did not seem to improve with higher dose, however. This study does little to compare the specific receptor effects, and certainly doesnt address anything about humans.

What one can surmise is that you could take a miniscule does of this stuff and have a similar effect to piracetam, but it could be easy to overshoot the ideal dose and potentially cancel out any benefit. This is something I've experienced with Noopept as well. High doses provide me with an anxiolytic but almost antinootropic effect. I expect this could be similar with Sunifiram. The potential advantage would be lower cost (unlikely for now) or less powder to manage while traveling, for example.

The concerns I have are that there is no safety profile or pharmacokinetic data on this drug. No ones knows the half life, thus what the frequency of dosing should be. Things like that... I may try a small amount, as it seems to be safe short term, but I certainly wouldn't consider it a replacement for Piracetam.

As a side note- the efficacy vs potency discussion I mention above is something I've only recently been considering in the context of racetams... I had not been aware of the possible bell shaped efficacy curve, but I have experienced it subjectively in my own experimentation. If anyone has literature on this, I would appreciate a referal. While merely anecdotal, this is further evidence in support of simply using high dose, low potency Piracetam as my sole racetam, as it may have the most flexible and tolerant therapeutic window.

This is, in fact, what I've been doing recently, and with great success. I've also reintroduced a new brand of ALCAR to my stack, which I feel has been providing a very positive benefit. Despite the trouble I've had with it in the past, the NOW brand has me feeling great, with no acne, allergy, weight gain, or fatigue like I had experienced previously. I've also tapered down and eliminated Ginkgo temporarily. I'm concerned about post synamptic NorEpi downregulation, and would like to give my neurons a chance to retore these receptors to an optimal level with planned resumption of Ginkgo a few weeks before my board exam.

For now this is my stack:

500mg ALCAR -BID/TID
1200-1600mg Piracetam - BID/TID
1000mg Cod Liver Oil -QD
100mg Phosphatidylserine - QD
1 scoop Spark - QD


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#123 NoopMed

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Posted 24 March 2013 - 01:03 AM

BTW sorry for some typos on that last one... I'm writing from a smart phone.

#124 PTShapeShifter

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Posted 24 March 2013 - 02:26 AM

Many thanks, NoopMed. Your post is extremely helpful, balanced and detailed with both information and balanced scientific & personal judgement.

In case you or anyone is shopping around for a trial of the Sunifiram, NewStarNootropics just started carrying it this week as well ~ pretty low unit cost at a 1000X Piracetam dose comparison. But with only rat study data to go by currently, and your perspective on the importance of understanding a drug's potency vs nootropic efficacy, I am planning going to wait for some human research before trying Sunifiram myself.

We would all certainly benefit from anyone here posting their case specific experience here if they decided to give it a trial. Many thanks again for the insights!

P.S. I'm having a full positive dose response with 500mg ALCAR from Swanson.

PTShapeShifter

#125 Sholrak

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Posted 25 March 2013 - 08:14 PM

NoopMed, as a medical student, what do you think about the Growth Factor potentiating substances, as Cerebrolysin (mainly), Lion's Mane, Pregnolenone, etc?

Looks like to me like the only "fair" way of getting any permanent benefits or changes. What would you say about the sfaety and convenience of this?

#126 jurassic

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Posted 26 March 2013 - 12:53 PM

Hi all,
this is my first post, I just had to write to say big thanks to NoopMed for this great thread and to all other people posting in forum. you make a great community, nice topics, and i find this most interesting and useful.

also i find it appropriate to post in this thread cause i'm also a med student, although i don't have the profound knowledge about nootropics yet, as i've only started experimenting few months ago, on and off, and have been lurking here.

my experience so far in summary is mostly with noopept, phenibut and centrophenoxine. i have been trying noots without real order, trying just to get a quick study aid for some acute situations. because of this i'm not sure what noot gave me what effect precisely. however, here's my summary so far:

I find noopept very interesting, but not precisely what i was looking for. on the plus side it gives energy, makes me more social and more talkative, gives a big boost to dream lucidity and dream recall. also, when i first took it, it gave me quite a rush, maybe a little manic in a way... also find it enhances sound enjoyment and vision.

however it doesn't help me study as i tend to loose focus more easily while i'm on it and it makes thinking more difficult in a way... like it inhibits prefrontal cortex a bit as alcohol would, you do things more, but you think about doing them less. messes up short term memory a bit... maybe

i'm not sure what to think about centro, as i have not been using it alone and i think i have had some side effects of too much acetylcholine cause i've been taking it with choline bitartrate, sometime in quite large amounts. i will experiment with it more in the future.

phenibut is a whole different story. i like it a lot, but still, it's not a real noot, and am planing on using it recreational and maybe for study aid in some nervous situations if i need to calm down. that being said, it has a most definite effect and is really nice if used in right way and not often. pretty dangerous stuff from what i read, with dependence and tolerance and everything.

effects so far have been mixed, sometimes i get too much stimulation so i can't focus, sometimes i get sleepy. sometimes i hit just the right spot :).

I'm still trying to find something to help me "passive study" - just sit there and concentrate on large stacks of materials, going through many information at once - acutely and short term. Any ideas? above mentioned noots are more useful for "active studying", when i have to communicate with other people or really do something like taking physical of a patient or discus differential diagnoses and treatment.

i have ordered aniracetam, pramiracetam, ALCAR, more noopept, centrophenoxine, phenibut... so i will experiment further and see what happens.

cheers

#127 blablabla

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Posted 26 March 2013 - 07:06 PM

Hey Noopmed,

Thanks for everything! I ordered your stack cause I give it a try. Also I ordered other supplements:


1
Doctor's Best, High Absorption CoQ10, 100 mg, 120 Veggie Caps(DRB-00188)
2
Now Foods, L-Tyrosine, 500 mg, 120 Capsules(NOW-00162)
3
Doctor's Best, Best Alpha Lipoic Acid, 150 mg, 120 Capsules(DRB-00104)
4
Cardiovascular Research Ltd., Magnesium Taurate, 180 Capsules(CVR-20106)
5
Nordic Naturals, Arctic Cod Liver Oil, Orange Flavor, 16 fl oz (473 ml)(NOR-54787)
6
Life Extension, Two-Per-Day Tablets, 120 Tablets(LEX-17151)
7
Now Foods, Ginkgo Biloba, 60 mg, 240 Vcaps(NOW-04684)
8
Jarrow Formulas, PS-100, Phosphatidylserine, 100 mg, 120 Capsules(JRW-16020)
iHerbs.com

Number 1,6,7 and 8 is from your stack. In place of piracetam, I will take aniracetam with DMAE or centro or choline bitartrate.
When I need an extra I will take little bit of noopept and for the exams vinpocetine.
Number 1 and 3: Somewhere I red that it was not bad for recovery purpose.
Number 2: Cause I quit smoking few weeks ago, it helps me little bit. For the first time I tried ALCAR 4days ago till today once a day (500mg,750mg,850mg and to day 500mg) but I'll never again take this! I was hell, like I just quited smoking, concentration problem etc.
Number 4 and 7: for several purpose.

I'm a noob. I started the first time in november'12 with piracetam and DMAE and it was OK, I had not bad score in january. Begin march I tried primaracetam 300mg but I didn't like it at all. I was a zombie and my testicals hurts!! The second day I took 100mg and my testicals hurts again. The third day I took 50mg. Same problem! I took primaracetam with alcar, alpha GPC(250mg and tyrosine(500mg). I dropped the primaracetam in the toilet (15gr)! Maybe was my problem due to something else but my reaction was proberly due to the bad conditioning! And yes I think it is, cause today I did'nt took the prima (toilet) and took the rest (alcar, CPD and tyrosine) and also I feel this pain (just left side of my left testical, maybe not the testical itself.) but a little less. After reading this afternoon about quiting smoking in combination with alcar I totally not try alcar tomorrow and maybe never again. I hope tomorrow this annoying feeling/"pain" will be gone! I red that nefiracetam can cause that problem on the testical! This paragraph could be another topic.

What do you think about the stack? I want also mention that every product mentioned here I have at my home.
In my stack are there things that not must be taken together? Like ALA and CoQ10?(morning?evening?)

My personal purpose is to give myself more motivation and possibilities for studying (science of economics) and to protect myself from further problems. In july I will not take these anymore untill begin november for 3 months again.

Have a nice evening!
Belgium, 8PM

#128 NoopMed

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Posted 26 March 2013 - 07:59 PM

Hi all,
this is my first post, I just had to write to say big thanks to NoopMed for this great thread and to all other people posting in forum. you make a great community, nice topics, and i find this most interesting and useful.

also i find it appropriate to post in this thread cause i'm also a med student, although i don't have the profound knowledge about nootropics yet, as i've only started experimenting few months ago, on and off, and have been lurking here.

my experience so far in summary is mostly with noopept, phenibut and centrophenoxine. i have been trying noots without real order, trying just to get a quick study aid for some acute situations. because of this i'm not sure what noot gave me what effect precisely. however, here's my summary so far:

I find noopept very interesting, but not precisely what i was looking for. on the plus side it gives energy, makes me more social and more talkative, gives a big boost to dream lucidity and dream recall. also, when i first took it, it gave me quite a rush, maybe a little manic in a way... also find it enhances sound enjoyment and vision.

however it doesn't help me study as i tend to loose focus more easily while i'm on it and it makes thinking more difficult in a way... like it inhibits prefrontal cortex a bit as alcohol would, you do things more, but you think about doing them less. messes up short term memory a bit... maybe

i'm not sure what to think about centro, as i have not been using it alone and i think i have had some side effects of too much acetylcholine cause i've been taking it with choline bitartrate, sometime in quite large amounts. i will experiment with it more in the future.

phenibut is a whole different story. i like it a lot, but still, it's not a real noot, and am planing on using it recreational and maybe for study aid in some nervous situations if i need to calm down. that being said, it has a most definite effect and is really nice if used in right way and not often. pretty dangerous stuff from what i read, with dependence and tolerance and everything.

effects so far have been mixed, sometimes i get too much stimulation so i can't focus, sometimes i get sleepy. sometimes i hit just the right spot :).

I'm still trying to find something to help me "passive study" - just sit there and concentrate on large stacks of materials, going through many information at once - acutely and short term. Any ideas? above mentioned noots are more useful for "active studying", when i have to communicate with other people or really do something like taking physical of a patient or discus differential diagnoses and treatment.

i have ordered aniracetam, pramiracetam, ALCAR, more noopept, centrophenoxine, phenibut... so i will experiment further and see what happens.

cheers



Hey there Jurassic, thanks for your post. I can corroborate most of how you describe Noopept. One thing I would ask is if you felt that it improved your studying in the long run, AKA the day after taking some, or in general after taking it for a period of time? I find that it does indeed harm my studying in the short term (acute effects of the drugs), but it is useful for more long term chronic use (perhaps at a lower dosage, and not taken as an "active" studying drug.) For example, I'm considering taking Noopept regularly in the evening, when I'm closing in on the end of my studying and plan to unwind with something relaxing/mildly stimulating then going to bed...

The following is an excerpt from a discussion I had about Noopept on Reddit with some fellow users when a user described feeling loss of short term memory and focus while taking it:


"I can corroborate this statement, in most respects. It mirrors my own experience with Noopept, however; I've used much shorter cycles--out of necessity. I'm a medical student with frequent exams (approx. every two/three weeks), and have found the most benefit from regular use during off weeks, with cessation of Noopept and concurrent increase in my Piracetam dose during exam week.

The short term inhibitory aspects of Noopept's action may be due to observations noted in this study:http://www.synaptolo...articles/36.pdf

It activates inhibitory signalling via GABA on hippocampal neurons--the neurons implicated most directly in short term memory. This signalling will reduce hippocampus activity in the short term, and perhaps lead to the experience of inhibited short term memory and focus.

Also, it should be noted that the primary study implicating Noopept as a potentially useful drug in cognitive improvement showed that BDNF/NGF (which are themselves signalling peptides) were actually DECREASED following acute dosage. Chronic dosage was required to show an increase, which seemed to continue to increase the longer it was used. On the other hand, mRNA encoding for BDNF and NGF was increased both immediately after dosage, and then increased to an even greater extent after chronic dosage (28 days, in this case... though for my own purposes, I wish they had sampled more frequently). This suggests that even acute dosage led to increased expression of these beneficial proteins, but that with simple acute dosage there might be some kind of short term breakdown of NGF/BDNF (in other words: the blueprint was made, but the factory [ribosomes] hadn't started building them at approximately 30 minutes after injection of the rats...and for some unknown reason the proteins were destroyed/modified somehow. BUT, if the rats were allowed to survive and continue receiving Noopept, the blueprints were made, and significant amounts of BDNF/NGF were made and found. Behavioral testing of these latter rats showed an increase in their intelligence compared to placebo treated rats... they got smarter).

I'm not sure if anyone knows enough about these neurotrophic proteins to predict how they will act in the short term on neurons, but overall; Noopept seems to beneficial for increasing brain function long term, while being inhibitory while actually in contact with your neurons. In other words, for the budding nootropics wizard: expect to be relaxed, and perhaps a worse test-taker and problem solver for 5-8 hours after you take Noopept. But, expect to slowly become smarter after the acute effects wear off (5-8 hours) when you take it more long term."

I have nothing to really comment on Phenibut, because I've never researched it nor taken it, and I'm not at a point where I really have the time/resources to try something new. From what I've heard, it's more of a direct stimulant, and I've got plenty of caffeine for that, so I never dug deeper.

From what I've been noticing lately (anecdotal segment here, as I've written on ALCAR neurochemistry in previous posts), ALCAR can sometimes act like Noopept for me, but in a less dramatic way in the short term. For a few hours after I take it, I notice some decrease in my active listening ability. I find myself becoming a bit distracted in conversations, etc. Converse to Noopept, I do have been retention when reading material than I normally do, even in the short term period after dosage. Overall, I've noticed a dramatic boost in my logic and reasoning abilities from ALCAR in the long term. It do not find it significantly helps either my short term or long term memory, but instead very strongly increases my decisiveness, abstract thinking, and pattern recognition. I can fly through complex problems and tasks at a much greater speed than I'm normally capable of, and in group discussions/debates/activities I become much more assertive and perceptive in the focused delivery of my logic and reasoning-- behind a particular patient case, for example. Long term this may be more along the lines of what you describe in terms of an "active" nootropic. As for "passive," I've found the combination of Piracetam, Ginkgo biloba, and slowly sipped caffeine to be the best in terms of powering through large amounts of information for many hours. Sometimes, I feel that Ginkgo can increase my state and trait anxiety levels, and I also find it can augment emotional perceptiveness--often to a point that becomes a hindrance. As I've moved away from book material and more towards patient and clinical work, Ginkgo has lost some of its usefulness for me for this reason.


Overall, Piracetam has been the most useful for both passive and active nootropic action. I think you'll find that Aniracetam has a very similar effect, sometimes with what seems to be a higher decrease of efficacy, but the problem I've always run into with Aniracetam is the very short half life. It only seems to last about 3 hours for me. I find it useful for a large, short-term boost, but it's not something I'm willing to manage on a regular basis, especially when its activity overlaps so closely with Piracetam.


As for centrophenoxine-- I'm not entirely convinced that I like/trust this drug. I found that on my first dose I got a very powerful headache that basically ruined the rest of my night of studying. I tried it again over the next few days, but earlier on in the day, and didn't get a headache, but sometimes got neck pain/stiffness. I took a couple weeks away from centro, then took it again at the recommended dose and got a severe headache and neck stiffness once again within about 45 minutes. Each time, this almost felt like a drug-induced meningitis, which is the last thing I'm looking for. People also describe this feeling with either too much or too little acetylcholine/choline supplementation in combination with Piracetam. Centro breaks down into a plant auxin and DMAE. Who knows what that plant auxin does, but I wouldn't be surprised if some kind of hypersensitivity was involved. DMAE on the other hand is well understood as a strong acetylcholine pathway precursor with the possible side effects of causing demethylation of DNA and being a generalized methyl group scavenger. This is a concern for many people taking it long term, and some people propose taking it with SAM-e for this reason-- as SAM-e is a good (but rather $$$) methyl group donor. The biggest advantage to Centro that I've read about has been the reduction/elimination of lipofuscin pigments from neurons, which gather with age. ALCAR/ALA supplements have also been shown to do this, and seem a safer alternative.

In the end, the most import thing I can suggest after reading your post is to formulate a dosing schedule and stick to it for a decent period of time so you have an ability to really judge the effects and benefits/adverse effects you experience. Another option is to start with something on it's own, settle in for a week or two, then add things one at a time. Because many of these nootropics have proved to have different effects on different people-- particularly the racetams-- the most important thing you can do is really gain a clear idea of how each one is effecting you and tailor your dose and stack to what works best.

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#129 jurassic

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Posted 26 March 2013 - 11:22 PM

Hey there Jurassic, thanks for your post. I can corroborate most of how you describe Noopept. One thing I would ask is if you felt that it improved your studying in the long run, AKA the day after taking some, or in general after taking it for a period of time? I find that it does indeed harm my studying in the short term (acute effects of the drugs), but it is useful for more long term chronic use (perhaps at a lower dosage, and not taken as an "active" studying drug.) For example, I'm considering taking Noopept regularly in the evening, when I'm closing in on the end of my studying and plan to unwind with something relaxing/mildly stimulating then going to bed...



well, i liked this topic in the first place cause your experience with noopept seemed similar to my so wanted to point that out. thanks again for all the posts here and elaborate discussion. i haven't been able to stick to some schedule of taking noopept or any other nootropic so far because of my unorganized lifestyle and impatient personality. on the other hand, most of this drugs are not around long enough for me to be sure their long term effect is safe. this is why I would really like to find a stack that would do something quick and certain, at least in the beginning. in the long term i might stick to some regime, but rapidly trying out different things is more of a first phase.

I have nothing to really comment on Phenibut, because I've never researched it nor taken it, and I'm not at a point where I really have the time/resources to try something new. From what I've heard, it's more of a direct stimulant, and I've got plenty of caffeine for that, so I never dug deeper.


i can't say i'm certain what effect it has, but at the moment i think phenibut is relaxing and anti-depressive in small dosages, with a mild mood lifting touch. at large doses it seems to get pretty strong with manic and stimulant feeling. i'm sure i will find lots of use for it in different situations. try it, you wont regret it. ;)

From what I've been noticing lately (anecdotal segment here, as I've written on ALCAR neurochemistry in previous posts), ALCAR can sometimes act like Noopept for me, but in a less dramatic way in the short term. For a few hours after I take it, I notice some decrease in my active listening ability. I find myself becoming a bit distracted in conversations, etc. Converse to Noopept, I do have been retention when reading material than I normally do, even in the short term period after dosage. Overall, I've noticed a dramatic boost in my logic and reasoning abilities from ALCAR in the long term. It do not find it significantly helps either my short term or long term memory, but instead very strongly increases my decisiveness, abstract thinking, and pattern recognition. I can fly through complex problems and tasks at a much greater speed than I'm normally capable of, and in group discussions/debates/activities I become much more assertive and perceptive in the focused delivery of my logic and reasoning-- behind a particular patient case, for example. Long term this may be more along the lines of what you describe in terms of an "active" nootropic. As for "passive," I've found the combination of Piracetam, Ginkgo biloba, and slowly sipped caffeine to be the best in terms of powering through large amounts of information for many hours. Sometimes, I feel that Ginkgo can increase my state and trait anxiety levels, and I also find it can augment emotional perceptiveness--often to a point that becomes a hindrance. As I've moved away from book material and more towards patient and clinical work, Ginkgo has lost some of its usefulness for me for this reason.

Overall, Piracetam has been the most useful for both passive and active nootropic action. I think you'll find that Aniracetam has a very similar effect, sometimes with what seems to be a higher decrease of efficacy, but the problem I've always run into with Aniracetam is the very short half life. It only seems to last about 3 hours for me. I find it useful for a large, short-term boost, but it's not something I'm willing to manage on a regular basis, especially when its activity overlaps so closely with Piracetam.


i understand that piracetam might be the best all around noot, i didn't try it yet because of a completely paramedical reason - being afraid of costume services not allowing it to pass cause i would need a large amount of it as it is taken in relatively big doses. probably will try it some day :). i will incorporate ginkgo in my routine, forgot to mention it. can't say it does some noticeable effect on it's own, but it comes in combination with lots of vitamins, good fatty acids and stuff so i'll take those pills. can't hurt. also, i agree with you about taking an energy drink for all those vitamins and precursors and better caffeine source than coffee.

about ALCAR, i intend to cycle it with centrophenoxine based on my daily routine. for example, i exercise every other day so i had the idea ALCAR might help there as well. i'm not sure how it changes hormonal balance yet, didn't read anything definite. any ideas?


As for centrophenoxine-- I'm not entirely convinced that I like/trust this drug. I found that on my first dose I got a very powerful headache that basically ruined the rest of my night of studying. I tried it again over the next few days, but earlier on in the day, and didn't get a headache, but sometimes got neck pain/stiffness. I took a couple weeks away from centro, then took it again at the recommended dose and got a severe headache and neck stiffness once again within about 45 minutes. Each time, this almost felt like a drug-induced meningitis, which is the last thing I'm looking for. People also describe this feeling with either too much or too little acetylcholine/choline supplementation in combination with Piracetam. Centro breaks down into a plant auxin and DMAE. Who knows what that plant auxin does, but I wouldn't be surprised if some kind of hypersensitivity was involved. DMAE on the other hand is well understood as a strong acetylcholine pathway precursor with the possible side effects of causing demethylation of DNA and being a generalized methyl group scavenger. This is a concern for many people taking it long term, and some people propose taking it with SAM-e for this reason-- as SAM-e is a good (but rather $$$) methyl group donor. The biggest advantage to Centro that I've read about has been the reduction/elimination of lipofuscin pigments from neurons, which gather with age. ALCAR/ALA supplements have also been shown to do this, and seem a safer alternative.

In the end, the most import thing I can suggest after reading your post is to formulate a dosing schedule and stick to it for a decent period of time so you have an ability to really judge the effects and benefits/adverse effects you experience. Another option is to start with something on it's own, settle in for a week or two, then add things one at a time. Because many of these nootropics have proved to have different effects on different people-- particularly the racetams-- the most important thing you can do is really gain a clear idea of how each one is effecting you and tailor your dose and stack to what works best.


i have not have any side effects so far, so that's not an issue here. i did have some excessive saliva excretion, when i think of it, but i'm not sure from centro or noopept or too much choline... i understand centro is best for older neurons, but i thought about taking it mainly just for the cholin supplementation part that is advised with racetams. i figured if it has some other actions, that's just a bonus. i've never heard about this demethylising DNA property, sure doesn't sound nice as I like my DNA methylated, and i will look into it more. i don't know what to think of it atm.

so, i was going for some combos here. aniracetam should be more relaxing and for quick "passive" study aid with centro, ginko and maybe some phenibut. if it would be too sedating, than add prami or change centro for ALCAR which should be more stimulating. "active" would be ALCAR, prami, noopept, maybe ani... i'll see how it works and adjust accordingly.

#130 sunjet

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Posted 03 April 2013 - 02:30 PM

NoopMed, what about Vinpocetine? Did you tried it?

At start you said that you don't understand how people take 1g Piracetam , but in your recent stack you wrote that you take 1,2-1,6 g per day ? What made you change your mind?

#131 NoopMed

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Posted 03 April 2013 - 02:57 PM

I believe at the start I said something along the lines of "i dont understand how people can take a gram of GINKGO and 12 grams of PiRACETAM at a time." I still feel that way. 1 gram of Piracetam in one dose is great, and somewhere in the range of 800mg-2g is what shows predictable, postive nootropic effects in most of the studies. Initially I probably expressed concern over the danger of high dose piracetam... After further research I would retract my concerns over danger, as at even very high doses (30 grams a day) it appears to remain safe...HOWEVER, at those high doses some studies seem to show a predominance of Piracetams anxiolytic effects, ie somnelence, sleepiness, etc. I also experience this at high doses, but a dose of 1-2 grams in the morning, and a few periodic doses of 600-800mg every 4-5 hours seems to work best for me. I still feel that very high doses of Ginkgo are probably dangerous, and could contribute to cerebral bleeds, for example. This is mostly because of the anticoagulant effects, coupled with the increased cerebral blood flow attributed to this herb.

I like vinpocetine, and the studies I've read suggest some good potential. The reason I don't use it regularly is because it has a very short half life, and I only get reasonable effects for a few hours, then I need to take more or I tend to have a refractory period of mental slowness. Over time it also depletes dopamine at axon terminals, and potentially other neurotransmitters, by the proposed mechanism of interfering with axonal NT transport proteins. With chronic use, it has been suggested this could lead to a reversible depression lasting a few weeks after cessation of the drug. I also get some itchiness when I take it, and as the drug is derived from vinca alkaloids of a periwinkle plant this could be some kind of allergic hypersensitivity. I tend to be prone to atopy, so that's another reason I avoid chronic use.

I still take it at about 5mg doses every once in a while for a short boost, and I also find that it will supress mild caffeine + piracetam motor tremors, aka "jitteriness." So that's another consideration, but the situation for its use does not often present itself to me. For the reasons above, I will never use it as part of a daily stack, but it's not something I would strongly advise against either...

#132 sunjet

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Posted 03 April 2013 - 03:33 PM

I talked with a very good professor, right now, in pharmaceutics and thats what he said about you stack

500mg ALCAR -BID/TID
1200-1600mg Piracetam - BID/TID
1000mg Cod Liver Oil -QD
100mg Phosphatidylserine - QD
1 scoop Spark - QD



ALCAR is helping only with Placebo, cold Liver is ok for your organism , but nothing special for the memory/cognitive stuff. Phosphatidylserine is ok. And the piracetam dose is very high, it's ok to go only with 400-500mg TID . He also said that the best combo possible of all this for healthy peers for memory/cognition is Phezam (combination of Piracetam 400mg and Cinnarizine 5mg) TID for a minimum of 2 months for effects. And Ginkgo is useless, in realirty it has no effects.

All other suppliments are just minor for the brain like Carnitine, Serine, B-Vitamins, Mg and Fish Oil, are good just for entire body, but how you said you like something straight forwarded on the brain only (memory , cognition). And for this, he only said that is this combo of Phezam OR you can get same results with piracetam 400mg TID + Vinpocetine 5mg BID, but best is the one above.

What do you think about this?

Edited by sunjet, 03 April 2013 - 03:49 PM.


#133 NoopMed

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Posted 03 April 2013 - 10:46 PM

I've actually got quite a lot to comment in response, but I'm studying for a pending exam right now and it will have to wait until this weekend. Basically, I don't dispute the additonal drugs he suggests, but I do dispute his claim about Ginkgo (a claim shared by many higher ups in the field that is based on some research that's a bit inconclusive and outdated, but highly cited) and would argue that it actually serves some overlapping purpose with Cinnarizine without the antidopiminergic side effects. In regard to Piracetam, some studies suggest it is no different than placebo below 1400mg. I'm not entirely convinced of that, but I notice a greater benefit in that dosage range. ALCAR is a whole other story, I don't think it's placebo, but I do think the benefit I've discovered from it is not directly related to active dosing, and I consider it part of my rest, recovery, and washout regimen. I have more thoughts on that to share later, but suffice to say, I plan to use it at high dose for short periods on "rest" days.

I'm curious what field your professor works in, or what his/her research/teaching focuses on...

Also, I'm closing in on my final board prep stack, so I'll have that up here soon.

Back to the books I go!

#134 sunjet

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Posted 03 April 2013 - 11:33 PM

My professor is teaching in my University , General and Clinical Pharmaceutics.

Can you show me the studies of the Piracetam-placebo thing ?


P.S: Check you PM, when you'll be free.

#135 evdvbr

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Posted 04 April 2013 - 07:24 PM

Hi NoopMed.

Great work you is doing here, thanks.

Can you help me with a simple stack?

I am studying to a hard exame, with about 18 matters. I will need to read about 1000 pages for each discipline.
I will study for around 14 months for the exame. It is a public selection for a high public job.

I need to work full time, 8 hours a week. So, I can only study after work and in the weekends.

My week average rate is 40 hours of study, most part of lecture and questions.

In the work-days I study around 5 hours, after work.
In the weekends and holiday, 10 hours/day.

What would be a good option for the work-days and for the weekends?

This week I statarded piracetam, 3x1200mg per day. The effects in me was incredible!

My memory is better, my focus is better and I'm not angry with noise from family while I'm sutdying,

Any help is very valued!

#136 Gnibja

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Posted 05 April 2013 - 04:39 PM

Noopmed, excellent stuff here. As an aspiring med student, slogging through undergraduate biology
, I was curious as to whether you had a final build following all of your ups and downs with various trials through school; something i could settle on and ride like a wave through the rest of my college career? I see that you value the bare minimum whereas most of these different threads promote megadosing of many noots at a time. I trust your credibility

#137 Major Legend

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Posted 07 April 2013 - 08:14 PM

Your post on noopept reflect exactly my documented experienced on Noopept. BDNF and NGF was really wonderful.

I wonder then is there any way to counter the inhibitory effects of Noopept on Hippocampal Neurons?

I did not like the signification impairment on working memory, which felt more like retardation. I note noopept also has a very stimulatory effect, which seems to disappear after the first 2 days or so.

I wonder why?

#138 fenra

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Posted 01 May 2013 - 01:35 AM

What do you think is the long term impact of piracetam on the kidney? To me it seems like the most interesting issue people could run into, given the forgivingness of every other known aspect of this drug and the physical doses this permits and implies.

I also often wonder about CILTEP, the forskohlii plant, cAMP, the liver, bile flow... this stack has always struck me as particularly taxing because of the feeling of tiredness it leaves me with. Then again, that might be caused by the caffeine component.

#139 NoopMed

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Posted 01 May 2013 - 01:43 AM

Hello All,

Sorry for the long delay since my last posting. As you may have already assumed, I've long since begun preparation for my board exams, so my time has been very limited and my schedule very inflexible. I wanted to jump on here real quickly to provide some info about recent additions and changes I've made to my stack, and to outline my finalized board studying/taking stack.

In the time since I've last written, I took the opportunity to explore Chemically Induced Long-term Potentiation (CILTP), which was pioneered in another Longecity thread by Abelard Lindsay. Lindsay's work can be found here: http://www.longecity...180#entry516792.

LTP boils down to the process by which our neurons create and strengthen synaptic connections. I can't outline it all in this context, but there's plenty of reading on Wiki about it, as well as in Lindsay's thread. CILTP has limited research backing it, but the results of what does exist are very promising. I can say from personal experience now that it has definitely augmented my stack by enhancing long term recall while studying, and improving focus and abstract reasoning while test-taking. The reason I chose to explore CILTP this late in the game was that I've actually been using a modified variant of a portion of Lindsay's stack the whole time-- albeit at a much lower, unintentional dose.

According to Lindsay, CILTP calls for the following:
"*Herbal PDE4 Inhibitor
one to two pills Now Foods Artichoke Extract *or* Source Naturals Activated Quercetin (1 or 2 pills max),
*cAMP increase
One Solaray Forskolin pill and
*Dopamine Source
2 or 3 Now Phenylalanine pills."

So, it turns out that Ginkgo biloba contains a substantial amount of Quercetin, which I realized after finding out that high dose quercetin was contraindicated on Natural Med. for combination therapy with high dose Ginkgo. My vitamin drink (Spark) also contains a substantial amount of L-Tyrosine (a metabolic intermediate following L-Phenylalanine on the way to making catacholamines. L-Phenylalanine is probably more efficacious, but I haven't tried it yet.). So, all I was really missing was the Forskolin to upregulate cAMP in the context of already inhibited cAMP degradation and ample Dopamine precursors. Not only does this additional upregulation of neuronal cAMP help eLTP and lLTP, but it also likely helps to ameliorate muscarinic acetylcholine receptor desensitization that is probably occurring to some extent with the amount of choline and piracetam I've been blasting through. This could be considered a partial cause of the gradual attenuation and reduced effectiveness of Piracetam that most people report, but no research has been done on this that I'm aware of... just my theory.

In addition to CILTP, I regret to admit that I've also been experimenting a bit in an area that I had hoped to avoid in this stack... stimulants. I've been trying out what is arguably the least addictive, most non-traditional stimulant: Armodafinil (aka, Nuvigil). This is the purified R-enantiomer of Modafinil, which is available by prescription for Narcolepsy, Shift-work sleep disorder, and other scenarios that require extended, alert, waking time without significant amphetamine side-effects. Feel free to read up on Wiki regarding the mechanisms. I actually find the benefits achieved from Nuvigil to be surprisingly limited. It keeps me awake and focused for a very long time, but that's about it. I don't feel extra energy (additional, i.e. caffeinated or adderal) and it does not improve my mental performance-- aside from negating the usual decline in performance that I associate with fatigue. If anything, it actually seems to reduce my testing performance on QBanks if I'm not careful to monitor my approach to the material. I find it makes me a bit more committal (perhaps impulsive?) when selecting an answer from multiple choice-- while normally I would spend a great deal of time ruling out alternative answers in the spirit of thoroughness. In conclusion, I'm not sure I find it very useful for test taking, but I do find it very beneficial for ridiculously extended study sessions: like the 12-14+ hour block study days I've been subjecting myself to for a while now. A word of caution here though with this one-- it's a prescription drug, which requires a legitimate reason to prescribe-- somehow board studying may be categorized as shift-work sleep disorder? Also, while the catacholamine reuptake effects of this drug are minimal when compared to traditional stimulants, great care should be taken for those with any kind of cardiac/cardiovascular condition. My blood pressure has been steady at 110/70, with an average HR of 70-80ish BPM throughout. Also, there is some potential for addiction and the building of tolerance, even if the FDA doesn't believe that to be so.

The final addition I've made is fairly straightforward: Claritin(loratadine), the OTC non-drowsy antihistamine. What most people forget about the antihistamines is that they're also antimuscarinic/anticholinergic. The reason "non-drowsy" antihistamines were made was because the original antihistamines (like benadryl) cross the blood brain barrier and inhibit neuronal histamine and acetylcholine receptors, which are involved in alertness, cognition, and memory. This lead to the side effect of drowsiness, etc, but also took care of allergies systemically. The invention of second generation antihistamines like Claritin prevented the cognitive side effects because the molecule cannot pass the blood brain barrier, or at least, only does so very, very minimally. The constant side effect that I periodically run into with nooptropics that enhance cholinergic signalling (all the choline precursors, ginkgo, and piracetam) was increased systemic cholinergic activity. Occasional mild bronchospasm, GI upset, sweating, muscle twitches, excess saliva, watery eyes, bradycardia, etc. I never experienced anything clinically concerning, but these are definitely annoying side effects. When I added in Armodafinil (a histamine agonist, among other things), I began noticing minor allergies and rashes-- as I've mentioned before I tend to be prone to atopy. The solution to both of these problems is the addition of a non-blood-brain-barrier soluble H1/M1,3 antagonist, like Claritin. Voila. No more systemic side effects and no noticeable reduction in CNS efficacy, the nootropic stack is now isolated to activity within the blood brain barrier... in theory. So far this has been working very well for me.

---------------------------------------------------

So here's my current Medical Boards Study Stack:

--Daily--

**Breakfast**
-120mg Ginkgo biloba
-1200mg Piracetam
-1 Scoop of Spark (500mg L-tyrosine, 500mg Choline bitartrate/citrate, 120mg caffeine, B vitamins, and other useful stuff.)
-1400mg Fish Oil (Containing 647 mg EPA, and 253mg DHA)
-1200mg Soy Lecithin
-250mg CDP-Choline
-500mg Quercetin
-25mg Forskolin (20% purified extract from in 125mg pill)
-10mg Loratadine

**Every 4.5 Hours After Breakfast**
(For me, this appears the be ideal time to re-dose Ginkgo and Piracetam and reinforce choline so that I have no reduction in performance.)
-800-1200mg Piracetam
-60mg Ginkgo biloba
-__X__ Choline Source (I've actually found the lecithin to be the most balanced, but I don't take it all the time due to high omega-6 fatty acid content, and my desire to keep a high omega-3 : omega-6 ratio for cardiovascular health. I find Alpha-GPC to be a bit strong for me, with some refractory dullness when it begins to wear off. Choline bitartrate is the mostly poorly absorbed, and while I find it to make a significant difference, it merely seems to maintain the baseline. Therefore I rotate, depending on the potency of choline precursor I need at the time. I'll switch between 300mg Alpha-GPC, 1200mg lecithin, and 500mg pure choline bitartrate-- these are listed in decreasing order of perceived effectiveness.)


Based on everything I've read, and from the last couple years of experimentation, the above combination appears to be effective, sustainable and healthy-- likely even longevity promoting. The addition of the CILTP component to the stack has been the only Nootropic addition I've made that has improved my exam scores beyond the core stack of Piracetam, Ginkgo, and Fish Oil, choline/phospholipids, and caffeine. (and I think I've tried just about every racetam derivative and nootropic herb out there...all of which have actually reduced my exam performance.) I noticed a difference within about 2 days, and it has been sustained. If anyone has any negative feedback on CILTP I'd love to hear about it, because it seems great. Thanks Abelard!

--------------------------------------
Additional Components:

In addition to the above I also use ALCAR (acetyl-L-carnitine), Calcium, Magnesium, and Vitamin D. I don't find the acute effects of ALCAR to be useful in cognition, but I do notice that if I take significant doses ~1000-1500mg per day for 2 days out of the month, I maintain a higher baseline performance in the context of the other components in this stack. Some researchers discuss the concept of a "carnitine pool" in which the 3 primary carnitines are continually modified and exchanged with eachother and possibly scavenged for use in other molecules-- like tearing off the acetyl group and plopping it onto choline... ALCAR also acts as a very important mitochondrial membrane transporter. I don't eat a lot of red meat (the primary source of ALCAR), so I theorize that my carnitine pool has a "slow leak," which can be ameliorated as such. Also, after further review of my diet, I do tend to be a bit short on magnesium, calcium, and vitamin D, therefore; I've also started taking a supplement of each of these approximately once a week.

So,

**Occasional Use**
1200 mg Calcium
500 mg Magnesium
1500 mg ALCAR
1000 iu Vitamin D

and finally,

**Rare Use**
-150mg Armodafinil (Taken early in the morning on a power-study day. Not taken on consecutive days.)



So there it is...

After about a year cruising (and then eventually contributing to) this forum and 2 years of medical school: there is my stack. In terms of results, the best I can offer is my exam performance, class rank, and general sense of well being. When I first started my medical education, I was scoring below average, not terrible, but enough to get me concerned. I started taking Ginkgo, and dabbled in Bacopa and Rhodiola as well. On daily Ginkgo, I was scoring right on the class average on exams and ranked right in the middle of the class for the first MD year. There are some confounding variables here, but Ginkgo made a modest improvement that was sustained in my view. With the addition of Piracetam, I quickly moved from the middle up to the top 5%, but this was not very well sustained and my performance was unpredictable. With the addition of choline sources and vigilance in monitoring my dose schedule I found nootropic homeostasis. I then began experimenting with other nootropics, which led to unpredictability and instability in my performance. My exam scores suffered, but not dearly, as I was still well above average. Upon returning to my tried and true core stack, I returned to the top 5% for several exams. With the addition of CILTP I moved into the top 1% for my last few exams, and also currently enjoy a greater subjective experience of predictability and regularity in my stack. The ups and downs that I once experienced with Ginkgo and occasionally with Piracetam are gone. Additionally, over the last 2 years I've gone from being a relatively introverted, anxious person and transformed into an outgoing, productive, and involved member of my class. Again, there's plenty of confounding evidence there, as medical school may simply foster that kind of experience for some people-- but there are certainly people in my class who do NOT have that outlook. There are a surprising number who have dropped out or failed out. Some people hate medical school, they see it as a obstacle in the way of their career and essentially an overwhelming, high stakes, high pressure living hell. For me, the experience has been challenging, but marked by edification, personal growth, and great success. I went from a dead-end job to a medical program that was way over my head, and with a little help, now sit firmly in the top of my class-- more content, more socially connected, and happier than I've ever been in my life. And, most importantly, I'm ready to tackle the boards!

This will probably be my last post for a while, as I've got an unimaginable amount of studying to do. I'm sorry I can't offer more direct help to people who have requested it, I only wish I had the time-- perhaps when I'm a licensed physician I'll be able to offer my help to this community in a more professional context (assuming I haven't converted to a full anti-malpractice defensive medicine mindset...^_^).

Thanks for all the input, thanks to all the other great threads and contributors on here, and many thanks to Longecity for fostering such a wonderful community!

Noopmed, out... For now.
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#140 NoopMed

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Posted 01 May 2013 - 01:48 AM

What do you think is the long term impact of piracetam on the kidney? To me it seems like the most interesting issue people could run into, given the forgivingness of every other known aspect of this drug and the physical doses this permits and implies.

I also often wonder about CILTEP, the forskohlii plant, cAMP, the liver, bile flow... this stack has always struck me as particularly taxing because of the feeling of tiredness it leaves me with. Then again, that might be caused by the caffeine component.



To my knowledge Piracetam is excreted unchanged by the kidney. As a small molecule with little innate activity, I don't anticipate any damage to the kidney and the long term high dose animal studies didn't find any. CILTP seems to leave me feeling very energized, though I agree with comments on the Abelard Lindsay thread that it seems to shorten the half life of caffeine. It is a bit of a liver load, but doesn't seem to pose a great threat to a healthy liver. My liver enzymes remain within normal limits. (ALT/AST)

#141 fenra

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Posted 01 May 2013 - 01:55 AM

To my knowledge Piracetam is excreted unchanged by the kidney. As a small molecule with little innate activity, I don't anticipate any damage to the kidney and the long term high dose animal studies didn't find any. CILTP seems to leave me feeling very energized, though I agree with comments on the Abelard Lindsay thread that it seems to shorten the half life of caffeine. It is a bit of a liver load, but doesn't seem to pose a great threat to a healthy liver. My liver enzymes remain within normal limits. (ALT/AST)


I see. Thank you sir! (And good luck with the studying)

Edited by fenra, 01 May 2013 - 01:56 AM.


#142 lostfalco

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Posted 01 May 2013 - 03:10 AM

Hey NoopMed, awesome thread! Very reasonable, intelligent suggestions...love it.

If you have a chance I would love to hear your thoughts on the dangers of this combo...d-cycloserine + tDCS. In studies 100mg D-CYC, taken two hours before stimulation, has been shown to prolong the effects of anodal tDCS (applied for 13 minutes) from 1 hour normally to over 24 hours in the motor cortex. Tbh, I can't believe they tested this in humans because it seems like the perfect recipe for excitotoxicity and apoptosis. However, anodal stimulation has been shown to double learning speed in multiple placebo controlled double blind studies and is the method used by DARPA in accelerated sniper training. Naturally, 24 hours of doubled learning speed (tDCS over the dlpfc increases WM, therefore possibly IQ esp in conjunction with dual n-back training) sounds pretty good but telling my entire dlpfc to commit suicide is unappealing! Your thoughts and extensive background knowledge would be greatly appreciated.

Main Source: Oxford Handbook of Transcranial Stimulation (2008) by Eric Wasserman...Chapter 17 (Michael A. Nitsche). And of course, there are numerous pubmed articles on the idea by Nitsche and others.

#143 NoopMed

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Posted 01 May 2013 - 04:09 AM

Hey NoopMed, awesome thread! Very reasonable, intelligent suggestions...love it.

If you have a chance I would love to hear your thoughts on the dangers of this combo...d-cycloserine + tDCS. In studies 100mg D-CYC, taken two hours before stimulation, has been shown to prolong the effects of anodal tDCS (applied for 13 minutes) from 1 hour normally to over 24 hours in the motor cortex. Tbh, I can't believe they tested this in humans because it seems like the perfect recipe for excitotoxicity and apoptosis. However, anodal stimulation has been shown to double learning speed in multiple placebo controlled double blind studies and is the method used by DARPA in accelerated sniper training. Naturally, 24 hours of doubled learning speed (tDCS over the dlpfc increases WM, therefore possibly IQ esp in conjunction with dual n-back training) sounds pretty good but telling my entire dlpfc to commit suicide is unappealing! Your thoughts and extensive background knowledge would be greatly appreciated.

Main Source: Oxford Handbook of Transcranial Stimulation (2008) by Eric Wasserman...Chapter 17 (Michael A. Nitsche). And of course, there are numerous pubmed articles on the idea by Nitsche and others.



I haven't really heard of this before, but the science behind it seems pretty developed and reasonable. Deep Brain Stimulation has certainly proven pretty miraculous for patients with Parkinson's, depression, etc, while stimulating elements of the basal ganglia mostly. I imagine this anodal tDCS to the prefrontal cortex would probably provide some interesting boost to active learning and exam performance, but it seems like it would be hard to accurately stimulate all levels of the brain involved in cognition d/t differences in neuron orientation and electrical field intensity with depth. Contact pads for stimulation also seem very imprecise. I wonder if anyone has ever tried deep brain stimulation of the hippocampus... or more interestingly to the nucleus basalis of Meynart, homeland of acetylcholine.

#144 lostfalco

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Posted 01 May 2013 - 02:09 PM

Hey NoopMed, awesome thread! Very reasonable, intelligent suggestions...love it.

If you have a chance I would love to hear your thoughts on the dangers of this combo...d-cycloserine + tDCS. In studies 100mg D-CYC, taken two hours before stimulation, has been shown to prolong the effects of anodal tDCS (applied for 13 minutes) from 1 hour normally to over 24 hours in the motor cortex. Tbh, I can't believe they tested this in humans because it seems like the perfect recipe for excitotoxicity and apoptosis. However, anodal stimulation has been shown to double learning speed in multiple placebo controlled double blind studies and is the method used by DARPA in accelerated sniper training. Naturally, 24 hours of doubled learning speed (tDCS over the dlpfc increases WM, therefore possibly IQ esp in conjunction with dual n-back training) sounds pretty good but telling my entire dlpfc to commit suicide is unappealing! Your thoughts and extensive background knowledge would be greatly appreciated.

Main Source: Oxford Handbook of Transcranial Stimulation (2008) by Eric Wasserman...Chapter 17 (Michael A. Nitsche). And of course, there are numerous pubmed articles on the idea by Nitsche and others.



I haven't really heard of this before, but the science behind it seems pretty developed and reasonable. Deep Brain Stimulation has certainly proven pretty miraculous for patients with Parkinson's, depression, etc, while stimulating elements of the basal ganglia mostly. I imagine this anodal tDCS to the prefrontal cortex would probably provide some interesting boost to active learning and exam performance, but it seems like it would be hard to accurately stimulate all levels of the brain involved in cognition d/t differences in neuron orientation and electrical field intensity with depth. Contact pads for stimulation also seem very imprecise. I wonder if anyone has ever tried deep brain stimulation of the hippocampus... or more interestingly to the nucleus basalis of Meynart, homeland of acetylcholine.

Thanks for your response. I know your time is very valuable.

tDCS definitely works. I've been using it for 3 years now with good effects. It's after effects are dependent upon the number of mA used, 1 or 2 in most studies, and the amount of time under stimulation...usually 20 minutes or so. Your brain stays stimulated for about an hour or two after. D-CYC is interesting because I would love to take it Sat morning at 8am, stimulate at 10am and then pull a 24 hour study binge to see how much I could learn...or how much I could improve my WM by doing dual nback for 24 hours. I'm not gonna fry my brain though, nor do I want to kill my gut biome with D-CYC. Do you know what kind of effect D-CYC would have on my gut?

Deep brain stim is very cool. The first external version of it was recently approved for Europe. It's called the Monarch and was developed by Dr. Christopher DiGiorgio at UCLA...http://www.neurosigma.com/. Will be interesting to see how this develops and if it has the same problems as surgical deep brain stimulation.

Sorry, don't mean to hijack your thread. Appreciate your insights.

#145 NoopMed

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Posted 01 May 2013 - 02:42 PM

Hey NoopMed, awesome thread! Very reasonable, intelligent suggestions...love it.

If you have a chance I would love to hear your thoughts on the dangers of this combo...d-cycloserine + tDCS. In studies 100mg D-CYC, taken two hours before stimulation, has been shown to prolong the effects of anodal tDCS (applied for 13 minutes) from 1 hour normally to over 24 hours in the motor cortex. Tbh, I can't believe they tested this in humans because it seems like the perfect recipe for excitotoxicity and apoptosis. However, anodal stimulation has been shown to double learning speed in multiple placebo controlled double blind studies and is the method used by DARPA in accelerated sniper training. Naturally, 24 hours of doubled learning speed (tDCS over the dlpfc increases WM, therefore possibly IQ esp in conjunction with dual n-back training) sounds pretty good but telling my entire dlpfc to commit suicide is unappealing! Your thoughts and extensive background knowledge would be greatly appreciated.

Main Source: Oxford Handbook of Transcranial Stimulation (2008) by Eric Wasserman...Chapter 17 (Michael A. Nitsche). And of course, there are numerous pubmed articles on the idea by Nitsche and others.



I haven't really heard of this before, but the science behind it seems pretty developed and reasonable. Deep Brain Stimulation has certainly proven pretty miraculous for patients with Parkinson's, depression, etc, while stimulating elements of the basal ganglia mostly. I imagine this anodal tDCS to the prefrontal cortex would probably provide some interesting boost to active learning and exam performance, but it seems like it would be hard to accurately stimulate all levels of the brain involved in cognition d/t differences in neuron orientation and electrical field intensity with depth. Contact pads for stimulation also seem very imprecise. I wonder if anyone has ever tried deep brain stimulation of the hippocampus... or more interestingly to the nucleus basalis of Meynart, homeland of acetylcholine.

Thanks for your response. I know your time is very valuable.

tDCS definitely works. I've been using it for 3 years now with good effects. It's after effects are dependent upon the number of mA used, 1 or 2 in most studies, and the amount of time under stimulation...usually 20 minutes or so. Your brain stays stimulated for about an hour or two after. D-CYC is interesting because I would love to take it Sat morning at 8am, stimulate at 10am and then pull a 24 hour study binge to see how much I could learn...or how much I could improve my WM by doing dual nback for 24 hours. I'm not gonna fry my brain though, nor do I want to kill my gut biome with D-CYC. Do you know what kind of effect D-CYC would have on my gut?

Deep brain stim is very cool. The first external version of it was recently approved for Europe. It's called the Monarch and was developed by Dr. Christopher DiGiorgio at UCLA...http://www.neurosigma.com/. Will be interesting to see how this develops and if it has the same problems as surgical deep brain stimulation.

Sorry, don't mean to hijack your thread. Appreciate your insights.



Cycloserine is an antibiotic that inhibits cell wall synthesis by interrupting the formation of peptidoglycan. Many antibiotics have this activity, the most commonly known being Penicillin. It looks like cycloserine is not an especially effective antibiotic, but it is still sometimes used to fight tuberculosis when other options fail. It was probably abandoned for the most part because of the CNS side effects. Regardless, taking it long term will indeed probably obliterate your enteric bacterial population (gut biome), potentially putting you at risk for horrible diarrhea from organisms like C-Diff and/or nutrient malabsorption. Additionally, main neurologic effect of cycloserine is partial antagonism of NDMA glutamate receptors. You're right to be concerned about excitotoxicity here.

Personally, I would avoid any kind of direct NDMA agonist. There's so much glutamate available in a healthy brain that there's little reason to provide an additional agonist to its receptors. More signal is not always better signal, more neuron activity does not correlate to improved cognition and intelligence. What does correlate is coordinated, organized firing patterns and efficient receptor and transmitter cycling. Drugs like Piracetam work by increasing the responsiveness of AMPA and NDMA channels to endogenous stimulii (glutamate). Elevated populations of astrocytes (cells that help neurons interconnect, maintain the blood brain barrier, and important to this context-- suck up and recycle glutamate) have been correlated to high IQ (this was supposedly the only significant finding in the dissection of Einstein's brain.) The idea behind tDCS, as I understood it, is to elevated the resting membrane potential of cortical neurons to a new baseline. In theory this allows them to reach threshold more quickly (after receiving excitatory input from glutamate) and depolarize more readily. It seems like the goal is to find the anodal current where you're near this threshold on average, but have not passed too far beyond it to the point where massive groups of neurons are spontaneously depolarizing. By introducing cycloserine it seems like you would be flooding the synapses with agonists to these receptors that cause post-synamptic neurons to fire in a way that is not correlated to pre-synaptic activity.... which is sounding an awful lot like a seizure-- which turns out to be one of the more serious side effects of cycloserine.

Have you tried using supplements like the racetams that allosterically modify NDMA/AMPA channels to make them more responsive? Have you tried any supplements that improve cerebral blood flow and glucose provision, like Vinpocetine or Ginkgo biloba? How about the CILTP stack-- which enhances the intracellular signal cascade that is activated by NDMA by upregulating and sustaining the expression of cAMP? These are all relatively safe options that will likely be much more effective in facilitating coordinated neural activity in the context of tDCS.

Also, I'm curious how you came by the equipment and training to run tDCS on yourself... Is this something one can easily do at home? Is it expensive?
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#146 lostfalco

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Posted 02 May 2013 - 01:40 AM

Thanks for all that great info on D-CYC, NMDA receptors, and neuroscience in general. I only mention D-CYC because it's actually been tested. Why would they use a 'partial' agonist instead of the full agonist? Which would be d-serine, right? Could glycine also be used? It binds to the same site as far as I know. It seems that the D-CYC somehow, "stabilizes the strengthening of receptors". Would d-serine or glycine stabilize the strengthening as well or does the fact that its a partial agonist matter? I'm clearly getting beyond my current depth here. ha Here's a study abstract. btw, I'm sure you're super busy...no worries if you don't have time to reply. This is kinda my pet interest anyway. =)

Neuropsychopharmacology. 2004 Aug;29(8):1573-8.
Consolidation of human motor cortical neuroplasticity by D-cycloserine.

Nitsche MA, Jaussi W, Liebetanz D, Lang N, Tergau F, Paulus W.

Source

Department Clinical Neurophysiology, Georg-August-University, Goettingen, Germany. mnitsch1@gwdg.de

Abstract


D-Cycloserine (CYC), a partial N-methyl-D-aspartate (NMDA) agonist, has been shown to improve cognitive functions in humans. However, the neurophysiological basis of this effect is unclear so far. We studied the impact of this drug on long-lasting after-effects of transcranial direct current (tDCS)-generated motor cortical excitability shifts, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials. While anodal tDCS enhances motor cortical excitability, cathodal tDCS diminishes it. Both effects seem to be NMDA receptor dependent. D-CYC selectively potentiated the duration of motor cortical excitability enhancements induced by anodal tDCS. D-CYC alone did not modulate excitability. The potency of this drug to consolidate neuronal excitability enhancements, most probably by stabilizing the strengthening of NMDA receptors, which is a probable neurophysiological derivate of learning processes, makes it an interesting substance to improve cognitive functions.

#147 lostfalco

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Posted 02 May 2013 - 01:51 AM

Hey NoopMed, awesome thread! Very reasonable, intelligent suggestions...love it.

If you have a chance I would love to hear your thoughts on the dangers of this combo...d-cycloserine + tDCS. In studies 100mg D-CYC, taken two hours before stimulation, has been shown to prolong the effects of anodal tDCS (applied for 13 minutes) from 1 hour normally to over 24 hours in the motor cortex. Tbh, I can't believe they tested this in humans because it seems like the perfect recipe for excitotoxicity and apoptosis. However, anodal stimulation has been shown to double learning speed in multiple placebo controlled double blind studies and is the method used by DARPA in accelerated sniper training. Naturally, 24 hours of doubled learning speed (tDCS over the dlpfc increases WM, therefore possibly IQ esp in conjunction with dual n-back training) sounds pretty good but telling my entire dlpfc to commit suicide is unappealing! Your thoughts and extensive background knowledge would be greatly appreciated.

Main Source: Oxford Handbook of Transcranial Stimulation (2008) by Eric Wasserman...Chapter 17 (Michael A. Nitsche). And of course, there are numerous pubmed articles on the idea by Nitsche and others.



I haven't really heard of this before, but the science behind it seems pretty developed and reasonable. Deep Brain Stimulation has certainly proven pretty miraculous for patients with Parkinson's, depression, etc, while stimulating elements of the basal ganglia mostly. I imagine this anodal tDCS to the prefrontal cortex would probably provide some interesting boost to active learning and exam performance, but it seems like it would be hard to accurately stimulate all levels of the brain involved in cognition d/t differences in neuron orientation and electrical field intensity with depth. Contact pads for stimulation also seem very imprecise. I wonder if anyone has ever tried deep brain stimulation of the hippocampus... or more interestingly to the nucleus basalis of Meynart, homeland of acetylcholine.

Thanks for your response. I know your time is very valuable.

tDCS definitely works. I've been using it for 3 years now with good effects. It's after effects are dependent upon the number of mA used, 1 or 2 in most studies, and the amount of time under stimulation...usually 20 minutes or so. Your brain stays stimulated for about an hour or two after. D-CYC is interesting because I would love to take it Sat morning at 8am, stimulate at 10am and then pull a 24 hour study binge to see how much I could learn...or how much I could improve my WM by doing dual nback for 24 hours. I'm not gonna fry my brain though, nor do I want to kill my gut biome with D-CYC. Do you know what kind of effect D-CYC would have on my gut?

Deep brain stim is very cool. The first external version of it was recently approved for Europe. It's called the Monarch and was developed by Dr. Christopher DiGiorgio at UCLA...http://www.neurosigma.com/. Will be interesting to see how this develops and if it has the same problems as surgical deep brain stimulation.

Sorry, don't mean to hijack your thread. Appreciate your insights.



Cycloserine is an antibiotic that inhibits cell wall synthesis by interrupting the formation of peptidoglycan. Many antibiotics have this activity, the most commonly known being Penicillin. It looks like cycloserine is not an especially effective antibiotic, but it is still sometimes used to fight tuberculosis when other options fail. It was probably abandoned for the most part because of the CNS side effects. Regardless, taking it long term will indeed probably obliterate your enteric bacterial population (gut biome), potentially putting you at risk for horrible diarrhea from organisms like C-Diff and/or nutrient malabsorption. Additionally, main neurologic effect of cycloserine is partial antagonism of NDMA glutamate receptors. You're right to be concerned about excitotoxicity here.

Personally, I would avoid any kind of direct NDMA agonist. There's so much glutamate available in a healthy brain that there's little reason to provide an additional agonist to its receptors. More signal is not always better signal, more neuron activity does not correlate to improved cognition and intelligence. What does correlate is coordinated, organized firing patterns and efficient receptor and transmitter cycling. Drugs like Piracetam work by increasing the responsiveness of AMPA and NDMA channels to endogenous stimulii (glutamate). Elevated populations of astrocytes (cells that help neurons interconnect, maintain the blood brain barrier, and important to this context-- suck up and recycle glutamate) have been correlated to high IQ (this was supposedly the only significant finding in the dissection of Einstein's brain.) The idea behind tDCS, as I understood it, is to elevated the resting membrane potential of cortical neurons to a new baseline. In theory this allows them to reach threshold more quickly (after receiving excitatory input from glutamate) and depolarize more readily. It seems like the goal is to find the anodal current where you're near this threshold on average, but have not passed too far beyond it to the point where massive groups of neurons are spontaneously depolarizing. By introducing cycloserine it seems like you would be flooding the synapses with agonists to these receptors that cause post-synamptic neurons to fire in a way that is not correlated to pre-synaptic activity.... which is sounding an awful lot like a seizure-- which turns out to be one of the more serious side effects of cycloserine.

Have you tried using supplements like the racetams that allosterically modify NDMA/AMPA channels to make them more responsive? Have you tried any supplements that improve cerebral blood flow and glucose provision, like Vinpocetine or Ginkgo biloba? How about the CILTP stack-- which enhances the intracellular signal cascade that is activated by NDMA by upregulating and sustaining the expression of cAMP? These are all relatively safe options that will likely be much more effective in facilitating coordinated neural activity in the context of tDCS.

Also, I'm curious how you came by the equipment and training to run tDCS on yourself... Is this something one can easily do at home? Is it expensive?


I have tried Piracetam, Vinpocetine, and Ginko. I have not tried CILTEP yet but Abelard encouraged me to try his most recent formulation and I will probably be doing that in the relatively near future.

I originally found an iontophoresis device on ebay for $50 but now I use this device...http://www.scriphessco.com/products/activa-activadose-ii-iontophoresis-device/

One of the best training videos that I have watched is this one...http://www.jove.com/video/2744/electrode-positioning-montage-transcranial-direct-current

This site also has a ton of great info...http://www.diytdcs.com/

#148 NoopMed

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Posted 02 May 2013 - 08:01 PM

To my knowledge Piracetam is excreted unchanged by the kidney. As a small molecule with little innate activity, I don't anticipate any damage to the kidney and the long term high dose animal studies didn't find any. CILTP seems to leave me feeling very energized, though I agree with comments on the Abelard Lindsay thread that it seems to shorten the half life of caffeine. It is a bit of a liver load, but doesn't seem to pose a great threat to a healthy liver. My liver enzymes remain within normal limits. (ALT/AST)


I see. Thank you sir! (And good luck with the studying)




After reviewing a few of the definitive pharmacokinetic reference sources on Piracetam, I just wanted to make a brief clarification here. Most common sources you read will say that Piracetam is completely handled by the kidneys and is urinated out completely unchanged. This is not absolutely accurate, but the statement is good enough in terms of how we want to think about the drug within the body, how to manage it, and how to dose it. The truth of the matter is that 90% of dosed Piracetam is reliably accounted for in the urine, and it is indeed completely unchanged. 10% basically cannot be accounted for, and for the most part nobody cares. The only thing people worry about is that because it's handled by the renal system, people with kidney failure need to take a lower dose to reach the desired plasma concentration.

This is splitting hairs, but I have a couple completely unsubstantiated theories about the other 10%... It's possible some is modified by the liver and excreted in a different form that researchers were unable to detect. It could be that the missing 10% simply stays in the body somehow. To explain the liver theory, one study did show that Piracetam DID inhibit the activity of a few cytochrome p450 enzymes in the liver, IN VITRO. This has never been demonstrated in vivo, and no liver enzyme elevation has been measured in vivo in long term studies-- so if it does become modified by the liver, it is probably a very minor change that would be nearly undetectable. No active metabolite has been found, but if the p450 system is involved, the modified version of Piracetam would probably be hydroxylated at a C-H site, turning it into C-OH. If we were to consider that second theory, that it stays in the body somehow... Some researchers believe that Piracetam is deposited into mitochondrial membranes, increasing their fluidity and efficiency. Perhaps the uptake of Piracetam into plasma membranes could account for this missing 10% in the urine. That's a longshot, but who knows. All of this is beyond my scope of knowledge, but my previous statement that Piracetam is renally excreted unchanged and has no known toxic effects on any organ system is still in concordance with accepted, peer reviewed literature.

This is a great resource for reading about drug pharmacodynamic and pharmacologic properties, btw:
http://toxnet.nlm.ni...m @rn 7491-74-9

#149 fenra

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Posted 02 May 2013 - 11:20 PM

After reviewing a few of the definitive pharmacokinetic reference sources on Piracetam, I just wanted to make a brief clarification here. Most common sources you read will say that Piracetam is completely handled by the kidneys and is urinated out completely unchanged. This is not absolutely accurate, but the statement is good enough in terms of how we want to think about the drug within the body, how to manage it, and how to dose it. The truth of the matter is that 90% of dosed Piracetam is reliably accounted for in the urine, and it is indeed completely unchanged. 10% basically cannot be accounted for, and for the most part nobody cares. The only thing people worry about is that because it's handled by the renal system, people with kidney failure need to take a lower dose to reach the desired plasma concentration.

This is splitting hairs, but I have a couple completely unsubstantiated theories about the other 10%... It's possible some is modified by the liver and excreted in a different form that researchers were unable to detect. It could be that the missing 10% simply stays in the body somehow. To explain the liver theory, one study did show that Piracetam DID inhibit the activity of a few cytochrome p450 enzymes in the liver, IN VITRO. This has never been demonstrated in vivo, and no liver enzyme elevation has been measured in vivo in long term studies-- so if it does become modified by the liver, it is probably a very minor change that would be nearly undetectable. No active metabolite has been found, but if the p450 system is involved, the modified version of Piracetam would probably be hydroxylated at a C-H site, turning it into C-OH. If we were to consider that second theory, that it stays in the body somehow... Some researchers believe that Piracetam is deposited into mitochondrial membranes, increasing their fluidity and efficiency. Perhaps the uptake of Piracetam into plasma membranes could account for this missing 10% in the urine. That's a longshot, but who knows. All of this is beyond my scope of knowledge, but my previous statement that Piracetam is renally excreted unchanged and has no known toxic effects on any organ system is still in concordance with accepted, peer reviewed literature.

This is a great resource for reading about drug pharmacodynamic and pharmacologic properties, btw:
http://toxnet.nlm.ni...m @rn 7491-74-9


Wow, thanks for that website!

I did read some years ago on Wikipedia that urine only contained 60% of the ingested Piracetam, so I guess new evidence adjusted that amount. To be honest, I always wondered if we sweat some of it out; I mean, isn't this stuff water soluble?

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#150 NoopMed

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Posted 02 May 2013 - 11:42 PM

It is water soluble. It's certainly a possibility. I would anticipate being able to smell it on your skin pretty distinctly if it was being sweated out in a substantial amounts. At doses of 800-1200mg per 4-5 hrs I can recognize its distinct smell in urine... not that I'm actively trying to smell my urine (lol) but it was something I noticed right off the bat with Piracetam. It's obviously a different kind of smell than something like asparagus, but I notice the smell to a similar "olfactory amplitude," if you want to call it that. I've never noticed smelling like piracetam after an intense workout, but I'll try to pay attention next time. Maybe someone could perform a Piracetam sweat test and get a publication. :)




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